It is found in some patent documents that a compound comprising a quinine structure is used for anti-cholinergic effect. For example, a compound disclosed in Chinese invention patent CN200810112248.1 and Chinese invention patent CN200910223255.3 has a structure as below, wherein: R is methyl, ethyl, propyl, isopropyl, or cyclopropyl; and X represents halogen atom.

French patent FR2012964 disclosed a structure as below, wherein: R is H atom, hydroxyl or alkyl with 1-4 carbon atoms; R1 is phenyl or thienyl; and R2 is cyclohexyl, cyclopentyl or thienyl.

U.S. Pat. No. 5,654,314 disclosed a structure as below:

WO Patent WO01/04118 disclosed a structure as below:

The above compounds have significant disadvantages, such as short-lasting efficacy, slow action, or significant toxic and side effects, or the like, in the treatment of rhinitis, post-cold rhinitis, chronic trachitis, airway hyperresponsiveness, asthma, chronic obstructive pulmonary diseases, cough, urinary incontinence, frequent urination, unstable bladder syndrome, bladder spasms, bladder inflammation and gastrointestinal diseases such as irritable bowel syndrome, spastic colitis, as well as duodenal and gastric ulcers.
The compounds of the present invention overcome the disadvantages of the above compounds, and in particular, are characterized by longer efficacy, rapid action, and lower toxic and side effects in the treatment of chronic trachitis, airway hyperresponsiveness, asthma, and chronic obstructive pulmonary diseases as compared with the compounds of prior art. Due to their good stability, the compounds of the present invention are suitable for manufacturing an inhalant that is administered once a day for treating chronic obstructive pulmonary diseases, and in particular, suitable for manufacturing a solution-type metered dose inhalation aerosol that is administered once a day. The present invention relates to the synthesis of said compound, the manufacture of a pharmaceutical composition comprising said compound and pharmaceutical uses thereof.
The compound of the present invention can also be used for treating the above respiratory diseases such as rhinitis, post-cold rhinitis, chronic trachitis, airway hyperresponsiveness, asthma, chronic obstructive pulmonary diseases, and the like, in combination with β2 receptor agonists, steroid hormone, antiallergic drugs, anti-inflammatory drugs, anti-infective drugs, phospholipase iv antagonists and the like.